Bile Acid Metabolism in Mammals. V. Studies on the Sex Difference in the Response of the Isolated Perfused Rat Liver to Chenodeoxycholic Acid

The hepatic metabolism of chenodeoxycholic acid (CDCA) was studied using the isolated perfused rat liver technique. In 12 perfusions, six male and six female, 30 μmol of CDCA were added to the perfusion medium, and in 12 other perfusions, also six of each sex, 1 μmol of CDCA was added to the perfusion medium. The CDCA was added after 2 h of base-line perfusion and the bile acids of liver, plasma, and bile were analyzed by combined thin-layer and gas chromatography. In the 2 h of perfusion prior to the addition of exogenous CDCA there were sex differences in the kinetics of bile acid secretion in the bile and in the bile acid composition of that bile. Following the addition of CDCA to the perfusion medium the female liver was found to take up more CDCA from the perfusion medium, to store more CDCA, and to convert less CDCA to β-muricholic acid. It was documented that the toxicity of CDCA for the isolated perfused liver of the female rat is not due to α- or β-muricholic acid, the end products of CDCA metabolism in the rat. The relatively greater capacity of the male liver to convert potentially toxic CDCA to nontoxic β-muricholic acid may explain, at least in part, the observed sex difference in CDCA hepatotoxicity.